key: cord-356127-xy5tyd7t
authors: Omidi, Negar; Forouzannia, Seyed Khalil; Poorhosseini, Hamidreza; Tafti, Seyed Hossein Ahmadi; Salehbeigi, Shahrzad; Lotfi‐Tokaldany, Masoumeh
title: Prosthetic heart valves and the COVID‐19 pandemic era: What should we be concerned about?
date: 2020-09-28
journal: J Card Surg
DOI: 10.1111/jocs.14707
sha: 
doc_id: 356127
cord_uid: xy5tyd7t

BACKGROUND: The disturbance in the international normalized ratio (INR) in patients receiving warfarin therapy is of concern. We aimed to evaluate coagulation features in hospitalized patients under warfarin treatment for prosthetic heart valves during the novel coronavirus disease 2019 (COVID‐19) pneumonia pandemic. METHODS: Between 20 February and 28 March 2020, 10 patients (7 males) who were under warfarin therapy for prosthetic heart valves were hospitalized after a diagnosis of COVID‐19 in Tehran Heart Center, Tehran, Iran. The clinical, paraclinical, and in‐hospital outcomes were described. The patients were followed for 4 weeks. RESULTS: The median age was 62 years. All the patients received antiviral treatment, either lopinavir/ritonavir or oseltamivir. The serum level of high‐sensitivity C‐reactive protein ranged between 0.24 and 15.24 mg/dL. Alanine aminotransaminase was normal in all the patients except for two, with levels 1.6 and 4.2 times above normal values. The INR increased in all the patients. One (10%) patient died in the hospital. No bleeding, ischemic, or thrombotic events occurred during the hospital stay and within the 4‐week follow‐up. CONCLUSIONS: Antiviral therapy in patients with COVID‐19 with prosthetic heart valves might be an issue responsible for an uncontrolled INR. Liver injury may happen in a minority of patients. Bridging in these patients during the antiviral treatment might be required and because of significant INR fluctuations, it might be safer to prescribe antiviral treatment in an inpatient setting.

Patients with prosthetic valve replacement with coronavirus disease 2019 (COVID- 19) infection are a challenging subset of patients to manage. Very little is known regarding the outcome of infection in these patients. The patients are challenging not just because of concomitant cardiovascular risk factors but also because of the presence of liver function abnormalities. Regular testing for the international normalized ratio (INR) in these patients who receive warfarin is critical, and meanwhile, concomitant infection is a great concern. It is already well-established that COVID-19 can not only cause atypical pneumonia and respiratory distress but also accompany abnormal liver function tests. Increased aspartate aminotransferase and alanine aminotransferase (liver enzymes) could be explained by the effect of COVID-19 on the liver itself and/or the prescription of antiviral therapies in hospitalized patients. [1] [2] [3] [4] [5] In the case of severe COVID-19 and the use of recommended antiviral therapies, such as lopinavir/ritonavir (KALETRA) and oseltamivir, a high INR is encountered in patients who use warfarin, even though without a change in the warfarin dosage. Very little is known about the interaction of anticoagulation drugs and antiviral drugs patients with prosthetic heart valves are often required to be treated with. Although interim guidance for the management of coagulopathy in patients with COVID-19 has been published, 6 the resultant clotting profile in patients with prosthetic heart valve are largely unknown. A consensus has yet to emerge as to the approach toward these patients with In this study, we describe a case series of patients with prosthetic heart valves and concomitant COVID-19 and seek to explore the challenges involving coagulation abnormalities. COVID-19 was confirmed by either real-time polymerase chain reaction (RT-PCR) assay or characteristic findings in chest computed tomography (CT). Of these, 10 patients had a prosthetic valve replacement and were enrolled in this study. The clinical, paraclinical, and in-hospital outcomes were recorded. Chest CT was done on a SIEMENS 16-slice CT scanner with a slice thickness of 5 mm, and the images were reviewed by a radiology specialist. Laboratory tests including the admission data of the white blood cell count; the percentage of lymphocytes; the levels of hemoglobin, alanine transaminase, aspartate aminotransferase, lactate dehydrogenase, and creatinine, and high-sensitivity C-reactive protein;

and RT-PCR results were recorded. The patients were followed for 4 weeks after hospital discharge.

Of the 10 patients, 7 (70%) were men, and the median age of all the patients was 62 years (range = 32-82 years). The demographic and clinical characteristics of each patient are listed in Table 1 . Four (40%) patients were smokers, and nine (90%) had at least one comorbidity. The most prevalent comorbidity was hypertension (50%).

All the patients had a prosthetic heart valve and were using warfarin.

KALETRA was prescribed for eight patients, and the other two T A B L E 1 Summary of the demographic and clinical characteristics and outcomes of the study patients with a prosthetic heart valve and novel Wuhan coronavirus pneumonia Table 2 Our observation revealed that 20% of the study patients had a liver injury, presented as increased alanine aminotransaminase, which is consistent with the results of the previous studies, 2 who reported 14-53% rate of liver injury among their patients during the hospital stay. As demonstrated previously, 40% of patients with COVID-19

were identified to have an increased INR and an elevated lactate dehydrogenase level during the course of the disease. 3, 5 It is suggested that increased lactate dehydrogenase has the potential to predict the severe form of the disease. 9 This enzyme was measured in six of our patients and exhibited a rise in four (66%) of them. Our only case of inhospital mortality had increased lactate dehydrogenase While COVID-19 presents with fever and other constitutional symptoms, the differential diagnosis of infectious endocarditis also has to be borne in mind in the presence of a prosthetic heart valve. In our study, four patients had a fever on admission, but none fulfilled the modified Duke criteria as a definite or suspected case for infectious endocarditis. 10 The interaction between antiviral treatment and warfarin is also of concern. Early reports were in favor of the important role of KALETRA in the treatment of the novel Wuhan viral pneumonia. 15 KALETRA is one of the protease inhibitors of cytochrome P450, administered to patients with COVID-19 to reduce the viral load. 16 An increase in the level of transaminase 7 days after KALETRA administration has been reported, 17 and the interaction between warfarin and KALETRA have been mentioned in previous cases. 17, 18 Possible interactions between oseltamivir and warfarin have also been reported, which could present with a rise in the INR. 19 Among our patients, eight were treated with KALETRA, and the other two patients were treated with oseltamivir.

At the same time, COVID-19 makes patients prone to the thrombotic state, which is a matter of great concern in patients with prosthetic heart valves. 

The salient limitation of this study is its small sample volume; accordingly, we would recommend larger scale studies with longer follow-ups to evaluate the prognostic factors of the severity and outcome of COVID-19 in patients with prosthetic heart valve infection.

The present study adds important insights into the outcome of COVID-19 in patients with a prosthetic heart valve. The current guidelines do not include a definite recommendation for bridging therapy in COVID-19 patients with a prosthetic heart valve. Bridging in these patients during the antiviral treatment course might be required and because of significant INR fluctuations, it might be safer to prescribe antiviral treatment in an inpatient setting. Coagulopathy in COVID-19 patients with a prosthetic heart valve in itself does not imply a poor prognosis.

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Prosthetic heart valves and the COVID-19 pandemic era: What should we be concerned about?

The authors would like to thank the staff of Tehran Heart Center and 

The authors declare that there are no conflict of interests.

Masoumeh Lotfi-Tokaldany http://orcid.org/0000-0001-8222-8794